TY - JOUR. T1 - Malonyl-CoA decarboxylase is not a substrate of AMP-activated protein kinase in rat fast-twitch skeletal muscle or an islet cell line. AU - Habinowski, Susan A.. AU - Hirshman, Michael. AU - Sakamoto, Kei. AU - Kemp, Bruce E.. AU - Gould, Stephen J.. AU - Goodyear, Laurie J.. AU - Witters, Lee A.. N1 - Funding Information: The authors thank Christopher Newgard (Southwestern) for the gift of the 832/13 cell line. This work was supported by an NIH grant (DK35712) awarded to L.A.W. and a grant from the American Diabetes Association to L.J.G. and L.A.W. B.E.K. is a NHMRC Australia Fellow. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2001/12/1. Y1 - 2001/12/1. N2 - The AMP-activated protein kinase (AMPK) plays an important role in fuel metabolism in exercising skeletal muscle and possibly in the islet cell with respect to insulin secretion. Some of these effects are due to AMPK-mediated regulation of cellular malonyl-CoA content, ascribed to the ability of AMPK ...

TY - JOUR. T1 - The Caenorhabditis elegans AMP-activated protein kinase AAK-2 is phosphorylated by LKB1 and is required for resistance to oxidative stress and for normal motility and foraging behavior. AU - Lee, Hyojin. AU - Jeong, Soo Cho. AU - Lambacher, Nils. AU - Lee, Jieun. AU - Lee, Se Jin. AU - Tae, Hoon Lee. AU - Gartner, Anton. AU - Koo, Hyeon Sook. PY - 2008/5/30. Y1 - 2008/5/30. N2 - AAK-2 is one of two α isoforms of the AMP-activated protein kinase in Caenorhabditis elegans and is involved in life span maintenance, stress responses, and germ cell cycle arrest upon dauer entry. We found that AAK-2 was phosphorylated at threonine 243 in response to paraquat treatment and that this phosphorylation depends on PAR-4, the C. elegans LKB1 homologue. Both aak-2 mutation and par-4 knockdown increased the sensitivity of C. elegans worms to paraquat, and the double deficiency did not further increase sensitivity, indicating that aak-2 and par-4 act in a linear pathway. Both mutations also ...

TY - JOUR. T1 - AMP-activated protein kinase regulates the expression of human telomerase reverse transcriptase. AU - Jo, Daum. AU - Park, Rackhyun. AU - Kim, Hyunju. AU - Jang, Minsu. AU - Lee, Eun Ju. AU - Jang, Ik Soon. AU - Park, Junsoo. N1 - Publisher Copyright: © 2018 Jo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.. PY - 2018/11. Y1 - 2018/11. N2 - The expression of hTERT in tumor cells contributes to oncogenic transformation by promoting immortalization. For this reason, hTERT is one of the major targets for cancer therapy, and an efficient method to downregulate hTERT expression is required for treatment of hTERT-positive cancer. In this report, we demonstrated that inhibition of AMP-activated protein kinase (AMPK) downregulates the expression of hTERT. We screened cell signaling pathways in ...

Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture.

Rationale: Elevated levels of C/EBP homologous protein (CHOP), a member of the C/EBP transcription factor family, in advanced atherosclerotic plaques is reported to be associated with atherosclerotic plaque rupture in humans. However, the molecular mechanism by which CHOP accumulation occurs is poorly defined. Objective: The aim of this study was to investigate if (1) macrophage AMP-activated kinase (AMPK) regulates cellular CHOP accumulation and (2) whole-body Ampk deletion leads to neointimal disruption. Methods and Results: In isolated or cultured macrophages, Ampkα1 deletion markedly increased apoptosis and CHOP, whereas pharmacological activation of AMPK dramatically reduced CHOP protein level via promoting CHOP degradation by proteasome. In addition, co-transfection of Chop-specific siRNA, but not control siRNA, markedly reduced apoptosis in macrophages transfected with Ampkα1-specific siRNA. Mechanistically, AMPKα1 was found to co-immunoprecipitate with CHOP and phosphorylate CHOP at ...

Alzheimer disease is an age-related neurodegenerative disorder characterized by amyloid-beta (Abeta) peptide deposition into cerebral amyloid plaques. The natural polyphenol resveratrol promotes anti-aging pathways via the activation of several metabolic sensors, including the AMP-activated protein kinase (AMPK). Resveratrol also lowers Abeta levels in cell lines; however, the underlying mechanism responsible for this effect is largely unknown. Moreover, the bioavailability of resveratrol in the brain remains uncertain. Here we show that AMPK signaling controls Abeta metabolism and mediates the anti-amyloidogenic effect of resveratrol in non-neuronal and neuronal cells, including in mouse primary neurons. Resveratrol increased cytosolic calcium levels and promoted AMPK activation by the calcium/calmodulin-dependent protein kinase kinase-beta. Direct pharmacological and genetic activation of AMPK lowered extracellular Abeta accumulation, whereas AMPK inhibition reduced the effect of resveratrol on Abeta

Because polyphenols may have beneficial effects on dyslipidemia, which accelerates atherosclerosis in diabetes, we examined the effect of polyphenols on hepatocellular AMP-activated protein kinase (AMPK) activity and lipid levels, as well as hyperlipidemia and atherogenesis in type 1 diabetic LDL receptor-deficient mice (DMLDLR−/−). In HepG2 hepatocytes, polyphenols, including resveratrol (a major polyphenol in red wine), apigenin, and S17834 (a synthetic polyphenol), increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC), and they increased activity of AMPK with 200 times the potency of metformin. The polyphenols also prevented the lipid accumulation that occurred in HepG2 cells exposed to high glucose, and their ability to do so was mimicked and abrogated, respectively, by overexpression of constitutively active and dominant-negative AMPK mutants. Furthermore, treatment of DMLDLR−/− mice with S17834 prevented the decrease in AMPK and ACC ...

Inactivating mutations in the protein kinase LKB1 lead to a dominantly inherited cancer in humans termed Peutz-Jeghers syndrome. The role of LKB1 is unclear, and only one target for LKB1 has been identified in vivo [3]. AMP-activated protein kinase (AMPK) is the downstream component of a protein kin …

Title: The Role of 5-AMP-Activated Protein Kinase (AMPK) in Diabetic Nephropathy: A New Direction?. VOLUME: 5 ISSUE: 1. Author(s):K. Wyatt McMahon, Dora I. Zanescu, Vineeta Sood, Elmus G. Beale and Sharma S. Prabhakar. Affiliation:Division of Nephrology and Hypertension, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.. Keywords:AMPK, diabetic nephropathy, enzyme regulation, molecular pathogenesis. Abstract: Diabetic nephropathy (DN) is a microvascular complication of diabetes that is characterized by proteinuria, glomerulosclerosis, and decreased kidney function ultimately leading to end stage renal disease; in fact, DN is the leading cause of end stage renal disease in the western world. Glycemic and blood pressure control are currently the most common forms of prevention and treatment of the disease. However, despite good glycemic and blood pressure control, many patients still progress to end stage renal disease and require renal ...

Hibernating animals develop fatty liver when active in summertime and undergo a switch to a fat oxidation state in the winter. We hypothesized that this switch might be determined by AMP and the dominance of opposing effects: metabolism through AMP deaminase (AMPD2) (summer) and activation of AMP-activated protein kinase (AMPK) (winter). Liver samples were obtained from 13-lined ground squirrels at different times during the year, including summer and multiples stages of winter hibernation, and fat synthesis and β-fatty acid oxidation were evaluated. Changes in fat metabolism were correlated with changes in AMPD2 activity and intrahepatic uric acid (downstream product of AMPD2), as well as changes in AMPK and intrahepatic β-hydroxybutyrate (a marker of fat oxidation). Hepatic fat accumulation occurred during the summer with relatively increased enzymes associated with fat synthesis (FAS, ACL and ACC) and decreased enoyl CoA hydratase (ECH1) and carnitine palmitoyltransferase 1A (CPT1A), rate limiting

Visfatin is an adipokine highly expressed in visceral AT (adipose tissue) of humans and rodents, the production of which seems to be dysregulated in excessive fat accumulation and conditions of insulin resistance. EPA (eicosapentaenoic acid), an n−3 PUFA (polyunsaturated fatty acid), has been demonstrated to exert beneficial effects in obesity and insulin resistance conditions, which have been further linked to its reported ability to modulate adipokine production by adipocytes. TNF-α (tumour necrosis factor-α) is a pro-inflammatory cytokine whose production is increased in obesity and is involved in the development of insulin resistance. Control of adipokine production by some insulin-sensitizing compounds has been associated with the stimulation of AMPK (AMP-activated protein kinase). The aim of the present study was to examine in vitro the effects of EPA on visfatin production and the potential involvement of AMPK both in the absence or presence of TNF-α. Treatment with the ...

Our study finds that coffee consumption or ex vivo treatment of cells with caffeine significantly improves migration of ECs and EPCs by an AMPK-dependent mechanism. Importantly, AMPK also contributed to the enhanced reendothelialization induced by caffeine in vivo. The beneficial influence of caffeine on reendothelialization seen in the mouse model could be explained by both migration of mature ECs as well as attachment of circulating EPCs, accelerating recovery of the endothelial monolayer. Several studies have documented the fundamental role of EPCs in the healing process of vascular endothelium alone,26 after mobilization with GM-colony stimulating factor (CSF),27 erythropoietin,28 or pretreatment with statins,3 estrogen29,30 or the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone.31 So far, two studies have investigated a potential role of AMPK for migration at least in mature ECs. Nagata et al have shown that overexpression of a dominant-negative mutant of the AMPK ...

Our study finds that coffee consumption or ex vivo treatment of cells with caffeine significantly improves migration of ECs and EPCs by an AMPK-dependent mechanism. Importantly, AMPK also contributed to the enhanced reendothelialization induced by caffeine in vivo. The beneficial influence of caffeine on reendothelialization seen in the mouse model could be explained by both migration of mature ECs as well as attachment of circulating EPCs, accelerating recovery of the endothelial monolayer. Several studies have documented the fundamental role of EPCs in the healing process of vascular endothelium alone,26 after mobilization with GM-colony stimulating factor (CSF),27 erythropoietin,28 or pretreatment with statins,3 estrogen29,30 or the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone.31 So far, two studies have investigated a potential role of AMPK for migration at least in mature ECs. Nagata et al have shown that overexpression of a dominant-negative mutant of the AMPK ...

Chronic fatigue syndrome: Exercise performance related to immune dysfunction. AMP-activated protein kinase: A key system mediating metabolic responses to exercise

Epidemiological studies have shown that infants exposed to an increased supply of nutrients before birth are at increased risk of type 2 diabetes in later life. We have investigated the hypothesis that fetal overnutrition results in reduced expression and phosphorylation of the cellular fuel sensor, AMP-activated kinase (AMPK) in liver and skeletal muscle before and after birth. From 115 days gestation, ewes were fed either at or 55% above maintenance energy requirements. Postmortem was performed on lamb fetuses at 139-141 days gestation (n = 14) and lambs at 30 days of postnatal age (n = 21), and liver and quadriceps muscle were collected at each time point. The expression of AMPK1 and AMPK2 mRNA was determined by quantitative RT-PCR (qRT-PCR). The abundance of AMPK and phospho-AMPK (P-AMPK) was determined by Western blot analysis, and the proportion of the total AMPK pool that was phosphorylated in each sample (%P-AMPK) was determined. The ratio of AMPK2 to AMPK1 mRNA expression was lower in ...

Activated AMPK promotes all the processes needed to maintain a youthful profile. However, AMPK activity fades with age. As previously mentioned, AMPK is activated in the presence of increased AMP. Therefore, to test the anti-aging properties of AMPK, researchers used fruit flies that were genetically engineered to synthesize higher levels of AMP. The research found that the modified flies lived up to one-third longer as a result of increased AMPK activity. The life span benefit of these mutations depends upon increased AMP:ATP and ADP:ATP ratios and adenosine monophosphate-activated protein kinase (AMPK). Transgenic expression of AMPK in adult fat body or adult muscle, key metabolic tissues, extended life span (Stenesen, 2013 ...

The present study is the first demonstration that administration of AICAR to insulin-resistant HF rats simultaneously increases glucose and FA uptake into skeletal muscle in close association with activation of AMPK. These effects occurred preferentially in white muscle and were consistent with the previously described improvement of insulin sensitivity in white muscle 24 h after AICAR treatment (8). Contrary to our initial speculation, there was no higher FA uptake in red muscle to balance the lack of AICAR effect on glucose uptake in this muscle type.. It is known that fluxes of glucose and FA into muscle are increased from the circulation during exercise (1,23,24). Recent studies have revealed an important role of AMPK in exercise-induced changes in fuel metabolism (1,2). However, many other factors are also important metabolic regulators in contracting muscle (7), such as decreased energy storage (ATP and creatine phosphate content) (25), increases in metabolic rate, muscle blood flow, and ...

Liver kinase B1 (LKB1), known as a serine/threonine kinase, has been identified as a critical cancer suppressor in many cancer cells. It is a master upstream kinase of 13 AMP-activated protein kinase (AMPK)-related protein kinases, and possesses versatile biological functions. LKB1 gene is mutated in many cancers, and its protein can form different protein complexes with different cellular localizations in various cell types. The expression of LKB1 can be regulated through epigenetic modification, transcriptional regulation and post-translational modification. LKB1 dowcnstream pathways mainly include AMPK, microtubule affinity regulating kinase (MARK), salt-inducible kinase (SIK), sucrose non-fermenting protein-related kinase (SNRK) and brain selective kinase (BRSK) signalings, etc. This review, therefore, mainly discusses recent studies about the expression, regulation, downstream signaling and cancer suppressive function of LKB1, which can be helpful for better understanding of this molecular and

The metabolic sensor, AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase existing as a heterotrimer of catalytic (α1/α2) and regulatory subunits (β1/β2 and γ1/γ2/γ3). The 12 possible heterotrimers exhibit tissue and potentially functional specificity [8], and all can be activated by binding of AMP/ADP to the AMPKγ subunit and phosphorylation by one of two upstream kinases, liver kinase B (LKB)1 or calcium/calmodulin-dependent protein kinase kinase (CaMKK)β. AMPK is activated in response to depletion of ATP or alterations in intracellular calcium concentrations, and acts to shut down ATP-consuming, anabolic pathways and promoting ATP-generating, catabolic pathways [9].. As a monitor of cellular and whole body energy status [10], it is probably unsurprising that a recent elegant study in Science from Reuben Shaws laboratory places AMPK at the heart of the regulation of mitochondrial dynamics. Using CRISPR modification to delete AMPKα1 and/or AMPKα2 in vitro, they ...

Background: The yeast SNF1 protein kinase and the mammalian AMP-activated protein kinase are highly conserved heterotrimeric complexes that are metabolic master switches involved in the switch from fermentative/anaerobic to oxidative metabolism. They are activated by cellular stresses that deplete cellular ATP, and SNF1 is essential in the response to glucose starvation. In both cases, activation requires phosphorylation at a conserved threonine residue within the activation loop of the kinase domain, but identifying the upstream kinase(s) responsible for this has been a challenging, unsolved problem. Results: Using a library of strains that express 119 yeast protein kinases as GST fusions, we identified Elm1p as the sole kinase that could activate the kinase domain of AMP-activated protein kinase in vitro. Elm1p also activated the purified SNF1 complex, and this correlated with phosphorylation of Thr210 in the activation loop. Removal of the C-terminal domain increased the Elm1p kinase ...

5-AMP-activated protein kinase subunit gamma-2 is an enzyme that in humans is encoded by the PRKAG2 gene. AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. Various forms of each of these subunits exist, encoded by different genes. AMPK is an important energy-sensing enzyme that monitors cellular energy status and functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This gene is a member of the AMPK gamma subunit family and encodes a protein with four CBS domains. Mutations in this gene have been associated with ventricular pre-excitation (Wolff-Parkinson-White syndrome), progressive conduction system disease and cardiac hypertrophy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. PRKAG2 has been shown to interact with PRKAB2 and PRKAB1. GRCh38: Ensembl release ...

AMP-activated protein kinase (AMPK) is a serine threonine kinase that is highly conserved through evolution. AMPK system acts as a sensor of cellular energy status. It is activated by increases in the cellular AMP:ATP ratio caused by metabolic stresses that either interfere with ATP production (eg, deprivation for glucose or oxygen) or that accelerate ATP consumption (eg, muscle contraction). Several upstream kinases, including liver kinase B1 (LKB1), calcium/calmodulin kinase kinase-beta (CaMKK beta), and TGF-beta-activated kinase-1 (TAK-1), can activate AMPK by phosphorylating a threonine residue on its catalytic alpha-subunit. Once activated, AMPK leads to a concomitant inhibition of energy-consuming biosynthetic pathways, such as protein, fatty acid and glycogen synthesis, and activation of ATP-producing catabolic pathways, such as fatty acid oxidation and glycolysis ...

Metformin is a biguanide antihyperglycemic that is approved for the management of type 2 diabetes mellitus. The mechanism by which metformin enhance insulin sensitivity are not fully characterized. At a molecular level, metformin may increase the activity of the enzyme adenosine monophosphate-activated protein kinase Metformin appears to suppress hepatic glucose output, decreased intestinal absorption of glucose, increased insulin mediated glucose utilization in peripheral tissues and has an antilypolytic affect on fatty acid concentration reducing gluconeogenesis . It does not produce hypoglycemia in either normal subjects or patients with type 2 diabetes. It is rapidly absorbed from the small intestine and without metabolism largely excreted in the urine. It is available in a generic form as 500 mg, 850mg and 1000 mg tablets. The target dose of metformin is in the range of 1500 mg to 2550mg . Metformin is given with meals to reduce the gastrointestinal side-effects. The most common ...

Ghrelin is a stomach-derived peptide that increases food intake through the activation of hypothalamic AMP-activated protein kinase (AMPK). However, the molecular mechanisms initiated by the activation of the ghrelin receptor, which in turn lead to A

AMP-activated protein kinase (AMPK) plays a major role in regulating cellular energy balance by sensing and responding to increases in AMP/ADP concentration relative to ATP. Binding of AMP causes allosteric activation of the enzyme and binding of either AMP or ADP promotes and maintains the phosphor …

5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) is an established pharmacological activator of AMP-activated protein kinase (AMPK). Both, AICAR and AMPK were reported to attenuate inflammation. However, AICAR is known for many AMPK-independent effects, although the mechanisms remain incompletely understood. Here we report a potent suppression of lipopolysaccharide (LPS)-induced inflammatory gene expression by AICAR in primary human macrophages, which occurred independently of its conversion to AMPK-activating 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl monophosphate. Although AICAR did not interfere with activation of cytosolic signalling cascades and nuclear translocation of nuclear factor - κB (NFκB) by LPS, it prevented the recruitment of NFκB and RNA polymerase II to target gene promoters. AICAR also inhibited signal transducer and activator of transcription 3 (STAT3)-dependent induction of interleukin (IL) IL-6 and IL-10 targets, while leaving STAT6 and HIF1α-dependent gene

Dive into the research topics of AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms. Together they form a unique fingerprint. ...

in Journal of Biological Chemistry (2011), 286(19), 16879-90. Extracellular Ca(2+) is essential for the development of stable epithelial tight junctions. We find that in the absence of extracellular Ca(2+), AMP-activated protein kinase (AMPK) activation and glycogen ... [more ▼]. Extracellular Ca(2+) is essential for the development of stable epithelial tight junctions. We find that in the absence of extracellular Ca(2+), AMP-activated protein kinase (AMPK) activation and glycogen synthase kinase (GSK)-3beta inhibition independently induce the localization of epithelial tight junction components to the plasma membrane. The Ca(2+)-independent deposition of junctional proteins induced by AMPK activation and GSK-3beta inhibition is independent of E-cadherin. Furthermore, the nectin-afadin system is required for the deposition of tight junction components induced by AMPK activation, but it is not required for that induced by GSK-3beta inhibition. Phosphorylation studies demonstrate that afadin is ...

The serine/threonine kinase LKB1 is a tumor suppressor gene mutated in the familial cancer condition Peutz-Jeghers syndrome (PJS), as well as in 30% of sporadic non-small cell lung cancer (NSCLC). One of the critical substrates of LKB1 is the AMP-activated protein kinase (AMPK). AMPK is a highly conserved sensor of cellular energy status found in all eukaryotic cells that restores metabolic homeostasis following stress. Thus LKB1 is a unique energy-state sensitive regulator of growth and metabolic reprogramming via its effects on AMPK. Our laboratory has performed a three-pronged screen to identify novel substrates of AMPK that may mediate its effects on metabolism and growth control. These studies have led to the identification of components of the mTOR signaling pathway (raptor, TSC2), the autophagy pathway (ULK1), and transcriptional regulators of metabolism (Srebp1, HDAC4/5/7) all as direct substrates of AMPK. Collectively, these studies uncovered novel conserved effectors of LKB1 and AMPK ...

THE BCA2 & AMPK PARADIGM: UNRAVELING THE CANCER CONNECTION By DANIELA (BUAC) VENTRO December 2013 Advisor: Dr. Q Ping Dou and Angelika M. Burger (deceased) Major: Cancer Biology Degree: Doctor of Philosophy Adenosine monophosphate-activated kinase (AMPK), a master regulator of cellular energy homeostasis, has emerged as a promising molecular target in the prevention of breast cancer, and phase II and III clinical trials using the FDA-approved, AMPK activating, anti-diabetic drug metformin are promising in this regard, but the question of why metformin is protective for some women but not others still remains. Breast Cancer Associated Gene 2 (BCA2/Rabring7/RNF115), a novel RING-finger ubiquitin E3 ligase, is overexpressed in |50% of breast tumors. Herein, I hypothesized that BCA2 is an endogenous inhibitor of AMPK activation in breast cancer cells and that BCA2 inhibition would therefore increase the efficacy of metformin. My hypothesis is strongly supported by the finding that BCA2 overexpression

From NCBI Gene:. The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. It is highly expressed in skeletal muscle and thus may have tissue-specific roles. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2013]. From UniProt: ...

Objective: To investigate the effect of lateral ventricle injection inhibitor nesfatin-1 on glycolipid metabolism and its relationship with hypothalamic AMPK expression. Methods: Nesfatin-1 was injected into the lateral ventricle of the rat by the brain stereotactic technique (nesfatin-1 group), and the sham operation group was injected with an equal volume of artificial cerebrospinal fluid and the control group had no interference factor. The rats were kept for 4 weeks and an automatic biochemical analyzer was used to detect blood sugar and blood lipid levels. The expression of AMPK mRNA in rat hypothalamus was detected by RT-PCR. The expression of AMPKα and phosphorylated AMPKα (pAMPKα) in the rat hypothalamus was detected by Western blot. Results: (1)According to the results of biochemical tests, compared to the control group, the level of FPG and TG in experimental group were significantly decreased (P ...

The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit is one of the gamma regulatory subunits of AMPK. Alternatively spliced transcript variants encoding distinct isoforms have been observed.[7] ...

This AMPK (A1/B2/G2) recombinant human protein (full length) was expressed in insect cells. AMPK (A1/B2/G2) serine/threonine kinase or AMP-activated protein kinase (AMPK) exhibits a key role as a master regulator of cellular energy homeostasis. AMPK exists as a heterotrimeric complex composed of a c

Statins are known to modulate cell surface cholesterol (CSC) and AMP-activated protein kinase (AMPK) in nonneural cells; however no study demonstrates whether CSC and AMPK may regulate simvastatin induced neuritogenesis (SIN). We found that simvastatin (SIM) maintains CSC as shown by Fillipin III staining, Flotillin-2 protein expression / localization and phosphorylation of various receptor tyrosine kinases (RTKs) in the plasma membrane. Modulation of CSC revealed that SIN is critically dependent on this CSC. Simultaneously, phospho array for mitogen activated protein kinases (MAPKs) revealed PI3K / Akt as intracellular pathway which modulates lipid pathway by inhibiting AMPK activation. Though, SIM led to a transient increase in AMPK phosphorylation followed by a sudden decline; the effect was independent of PI3K. Strikingly, AMPK phosphorylation was regulated by protein phosphatase 2A (PP2A) activity which was enhanced upon SIM treatment as evidenced by increase in threonine phosphorylation. ...

Results HD feeding plus low-dose STZ injection successfully induced T2DM. Compared to normal control, diabetic mice manifested higher fasting-blood glucose level, lower glucose tolerance in OGTT examination (n=12, p,0.05), but there was no difference in plasma insulin levels. RSV alleviated MI/R injury in both normal and diabetic mice, as evidenced by decreased infarct size, cardiomyocytes apoptosis, caspase-3 activity, improved cardiac function (n=10, all p,0.05). Moreover, RSV treatment improved APN level, upregulated APN multimerisation both in plasma and adipose tissue, and increased DsbA-L expression in adipose tissue in diabetic mice (all p,0.01). Conversely, administration of AMPK inhibitor Compound C significantly attenuated the cardioprotective effects of RSV (all p,0.05).. ...

Prkaa2 - Prkaa2 (GFP-tagged) - Mouse protein kinase AMP-activated alpha 2 catalytic subunit (Prkaa2), (10ug) available for purchase from OriGene - Your Gene Company.

All living cells require energy, usually provided in the form of ATP, to carry out fundamental processes like movement and growth. Therefore, cells have to balance energy supply with the demand. AMP-activated protein kinase (AMPK) has emerged as a central component of a signalling pathway involved in regulating intracellular energy homeostasis. When ADP and AMP levels increase, concomitant with a fall in ATP levels, AMPK is activated by phosphorylation on threonine-172 within the catalytic a subunit by upstream kinases including LKB1 and calcium/calmodulin protein kinase kinase (CaMKK) ß. Once activated, AMPK responds by phosphorylating downstream targets, the net effect of which is to switch off ATP-consuming processes and switch on ATP-producing processes. When the levels of nucleotides are restored to normal physiological concentrations, AMPK is inactivated by an unknown protein phosphatase(s). Major advances have been made over the last five years in understanding the molecular mechanism of how

Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3,5-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway. It should not be confused with 5-AMP-activated protein kinase (AMP-activated protein kinase ...

Objective: To investigate the effect and mechanism of CTRP13 on hepatic sinusoidal capillarization induced by high glucose in rat liver sinusoidal endothelial cells (rLSECs).Results: CTRP13 was reduced in high glucose-treated rLSECs. High glucose increased LN and CAV-1 expression and inhibited CaMKKβ and AMPK phosphorylation. CTRP13 overexpression protected rLSECs against high glucose-induced increase of LN and CAV-1 expression. Moreover, CTRP13 overexpression increased high glucose-induced inhibition of CaMKKβ and AMPK activation in CTRP13-overexpressing rLSECs. Inhibition of CaMKKβ and AMPK disturbed the protective effects of CTRP13 in high glucose-induced increase of LN and CAV-1. Hepatic steatosis was enhanced and basement membrane was thickened in liver of diabetic fatty liver rats.Conclusions: Our data identified the protective role of CTRP13 in hepatic sinusoidal capillarization induced by high glucose via activating CAMKKβ/AMPK pathway. CTRP13 may be a potential target

PubMed journal article Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling were found in PRIME PubMed. Download Prime PubMed App to iPhone, iPad, or Android

Author(s): Mo, Jung-Soon; Meng, Zhipeng; Kim, Young Chul; Park, Hyun Woo; Hansen, Carsten Gram; Kim, Soohyun; Lim, Dae-Sik; Guan, Kun-Liang | Abstract: YAP (Yes-associated protein) is a transcription co-activator in the Hippo tumour suppressor pathway and controls cell growth, tissue homeostasis and organ size. YAP is inhibited by the kinase Lats, which phosphorylates YAP to induce its cytoplasmic localization and proteasomal degradation. YAP induces gene expression by binding to the TEAD family transcription factors. Dysregulation of the Hippo-YAP pathway is frequently observed in human cancers. Here we show that cellular energy stress induces YAP phosphorylation, in part due to AMPK-dependent Lats activation, thereby inhibiting YAP activity. Moreover, AMPK directly phosphorylates YAP Ser 94, a residue essential for the interaction with TEAD, thus disrupting the YAP-TEAD interaction. AMPK-induced YAP inhibition can suppress oncogenic transformation of Lats-null cells with high YAP activity. Our study

HIGHLIGHTS: AMPK-dependent Raptor Ser792 phosphorylation does not influence mTORC1-S6K1 activation by intense muscle contraction. α2 -AMPK activity-deficient mice have lower contraction-stimulated protein synthesis Increasing glycogen activates mTORC1-S6K1 independently of AMPK α2 Normalizing muscle glycogen content rescues reduced protein synthesis in AMPK-deficient mice ABSTRACT: Objective The mammalian Target of Rapamycin Complex 1 (mTORC1)-S6K1 signalling pathway regulates muscle growth-related protein synthesis and is antagonized by AMP-activated protein kinase (AMPK) in multiple cell types. Resistance exercise stimulates skeletal muscle mTORC1-S6K1 and AMPK signalling and post-contraction protein synthesis. Glycogen inhibits AMPK and has been proposed as a pro-anabolic stimulus. The aim of this study was to investigate how muscle mTORC1-S6K1 signalling and protein synthesis respond to resistance exercise-mimicking contraction in the absence of AMPK and with glycogen-manipulation. Methods ...

Metabolix™ AMPK is an orthomolecular combination of ingredients that together contribute to AMPK activation with beneficial effects in Metabolic Syndrome.. Metabolic syndrome (MetS) is a cluster of health problems created by insulin resistance (IR) which include: fat accumulation (especially around the waist), high blood pressure, high triglycerides (blood lipids level), high blood sugar, and low good cholesterol (HDL). Together, they result in accelerated aging and an increased risk of coronary artery disease events such as heart attack, stroke, and diabetes. The good news is that apart from diet and exercise, scientific research has recently discovered that the enzyme 5′-AMP-activated protein kinase (AMPK) has a major role in the regulation of cellular lipid and protein metabolism. AMPK regulates glucose transport, lipid and protein synthesis, and fuel metabolism as well as other factors that have been linked to insulin resistance.. ...

NK cells are the first line of defense against infected and transformed cells. Defective NK cell activity was shown to increase susceptibility for viral infections and reduce tumor immune-surveillance. With age, the incidence of infectious diseases and malignancy rises dramatically, suggesting that impaired NK cell function might contribute to disease in these individuals. We found an increased frequency of NK cells with high expression of the inhibitory killer cell lectin-like receptor G1 (KLRG1) in individuals |70 y. The role of KLRG1 in ageing is not known, and the mechanism of KLRG1-induced inhibition of NK cell function is not fully understood. We report that NK cells with high KLRG1 expression spontaneously activate the metabolic sensor AMP-activated protein kinase (AMPK) and that activation of AMPK negatively regulates NK cell function. Pre-existing AMPK activity is further amplified by ligation of KLRG1 in these cells, which leads to internalization of the receptor and allows interaction with

NK cells are the first line of defense against infected and transformed cells. Defective NK cell activity was shown to increase susceptibility for viral infections and reduce tumor immune-surveillance. With age, the incidence of infectious diseases and malignancy rises dramatically, suggesting that impaired NK cell function might contribute to disease in these individuals. We found an increased frequency of NK cells with high expression of the inhibitory killer cell lectin-like receptor G1 (KLRG1) in individuals |70 y. The role of KLRG1 in ageing is not known, and the mechanism of KLRG1-induced inhibition of NK cell function is not fully understood. We report that NK cells with high KLRG1 expression spontaneously activate the metabolic sensor AMP-activated protein kinase (AMPK) and that activation of AMPK negatively regulates NK cell function. Pre-existing AMPK activity is further amplified by ligation of KLRG1 in these cells, which leads to internalization of the receptor and allows interaction with

PubMed journal article: Astragalus polysaccharide stimulates glucose uptake in L6 myotubes through AMPK activation and AS160/TBC1D4 phosphorylation. Download Prime PubMed App to iPhone, iPad, or Android

In this issue of the JCI, Zhou and coworkers provide evidence that the elusive target of metformins actions is the AMP-activated protein kinase (AMPK) (8). In studies performed in isolated hepatocytes and rat skeletal muscles, they demonstrate that metformin leads to AMPK activation, accompanied by an inhibition of lipogenesis (due to inactivation of acetyl-CoA carboxylase and suppression of lipogenic enzyme expression), suppression of the expression of SREBP-1 (a central lipogenic transcription factor), and a modest stimulation of skeletal muscle glucose uptake. Similar hepatic effects are seen in metformin-treated rats. Based on the use of a newly discovered AMPK inhibitor, their data suggest that the ability of metformin to suppress glucose production in hepatocytes requires AMPK activation. Many of these effects are similar to that of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a known, albeit nonspecific, activator of AMPK (9). However, metformin does not lead to AMPK activation ...

The heart relies predominantly on a balance between fatty acids and glucose to generate its energy supply. There is an important interaction between the metabolic pathways of these two substrates in the heart. When circulating levels of fatty acids are high, fatty acid oxidation can dominate over glucose oxidation as a source of energy through feedback inhibition of the glucose oxidation pathway. Following an ischaemic episode, fatty acid oxidation rates increase further, resulting in an uncoupling between glycolysis and glucose oxidation. This uncoupling results in an increased proton production, which worsens ischaemic damage. Since high rates of fatty acid oxidation can contribute to ischaemic damage by inhibiting glucose oxidation, it is important to maintain proper control of fatty acid oxidation both during and following ischaemia. An important molecule that controls myocardial fatty acid oxidation is malonyl-CoA, which inhibits uptake of fatty acids into the mitochondria. The levels of ...

In eukaryotic cells AMP-activated protein kinase (AMPK) plays a major role in regulating cellular energy balance. AMPK responds to changes in intracellular adenine nucleotide levels, being activated by an increase in AMP/ADP relative to ATP. Activation of AMPK increases the rate of catabolic (ATP-generating) pathways and decreases the rate of anabolic (ATP-utilising) pathways. In addition to its role in maintaining intracellular energy balance, AMPK regulates whole body energy metabolism. Given its key role in controlling energy homeostasis, AMPK has attracted widespread interest as a potential therapeutic target for metabolic diseases, including type 2 diabetes and, more recently, cancer. Here I review the regulation of AMPK and its potential as a target for therapeutic intervention in human disease ...

LKB1 was discovered as a tumour suppressor mutated in Peutz-Jeghers syndrome, and is a gene involved in cell polarity as well as an upstream protein kinase for members of the AMP-activated protein kinase family. We report that mammals express two splice variants caused by alternate usage of 3′-exons. LKB1L is the previously described form, while LKB1S is a novel form in which the last 63 residues are replaced by a unique 39-residue sequence lacking known phosphorylation (Ser431) and farnesylation (Cys433) sites. Both isoforms are widely expressed in rodent and human tissues, although LKB1S is particularly abundant in haploid spermatids in the testis. Male mice in which expression of Lkb1S is knocked out are sterile, with the number of mature spermatozoa in the epididymis being dramatically reduced, and those spermatozoa that are produced have heads with an abnormal morphology and are non-motile. These results identify a previously undetected variant of LKB1, and suggest that it has a crucial ...

We tested the hypothesis that repeated activation of AMPK induces mitochondrial and glucose membrane transporter gene/protein expression via a peroxisome proliferator activated receptor Upsilon co-activator (PGC)-1alpha dependent mechanism. Whole body PGC-1alpha knockout (KO) and littermate wild type (WT) mice were given either a single or repeated subcutaneous injection of the AMPK activator AICAR or saline. Skeletal muscles were dissected either 1h or 4h after the single AICAR treatment or 24h after the last injection following the repeated AICAR treatment. Repeated AICAR treatment increased GLUT4, cytochrome c oxidase (COX)I and cytochrome (cyt) c protein expression ~10-40% relative to saline in white muscles of the WT mice, but not of the PGC-1alpha KO mice. In line, GLUT4 and cyt c mRNA content increased 30-60% 4h after a single AICAR injection relative to saline only in WT mice. One hour after a single AICAR treatment, phosphorylation of AMP-activated protein kinase (AMPK) and the ...

Glycogen availability can influence glucose transporter 4 (GLUT4) expression in skeletal muscle through unknown mechanisms. The multisubstrate enzyme AMP-activated protein kinase (AMPK) has also been shown to play an important role in the regulation of GLUT4 expression in skeletal muscle. During contraction, AMPK [alpha]2 translocates to the nucleus and the activity of this AMPK isoform is enhanced when skeletal muscle glycogen is low. In this study, we investigated if decreased pre-exercise muscle glycogen levels and increased AMPK [alpha]2 activity reduced the association of AMPK with glycogen and increased AMPK [alpha]2 translocation to the nucleus and GLUT4 mRNA expression following exercise. Seven males performed 60 min of exercise at ~70% [VO.sub.2] peak on 2 occasions: either with normal (control) or low (LG) carbohydrate pre-exercise muscle glycogen content. Muscle samples were obtained by needle biopsy before and after exercise. Low muscle glycogen was associated with elevated AMPK ...

Inoki K., Zhu T., Guan K.L.. Mutations in either the TSC1 or TSC2 tumor suppressor gene are responsible for Tuberous Sclerosis Complex. The gene products of TSC1 and TSC2 form a functional complex and inhibit the phosphorylation of S6K and 4EBP1, two key regulators of translation. Here, we describe that TSC2 is regulated by cellular energy levels and plays an essential role in the cellular energy response pathway. Under energy starvation conditions, the AMP-activated protein kinase (AMPK) phosphorylates TSC2 and enhances its activity. Phosphorylation of TSC2 by AMPK is required for translation regulation and cell size control in response to energy deprivation. Furthermore, TSC2 and its phosphorylation by AMPK protect cells from energy deprivation-induced apoptosis. These observations demonstrate a model where TSC2 functions as a key player in regulation of the common mTOR pathway of protein synthesis, cell growth, and viability in response to cellular energy levels.. Cell 115:577-590(2003) ...

Thank you for your interest in spreading the word about Biochemical Society Transactions.. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.. ...

G protein-coupled estrogen receptor 1 (GPER1) is a seven-transmembrane receptor that mediates rapid cell signaling events stimulated by estrogens. While the role that GPER1 has in the modulation of E2-responsive tissues and cancers is well documented, the molecular mechanisms that regulate GPER1 expression are currently not well defined. The recently identified GPER1-dependent mechanism of tamoxifen action in breast cancer cells underscores the importance of identifying mechanisms that regulate GPER1 expression in this cell type. We hypothesized that GPER1 expression in breast cancer cells is sensitive to [D-glucose] and provide data showing increased GPER1 expression when cells were cultured in low [D-glucose]. To determine if the observed accumulation of GPER1 was AMP-activated protein kinase (AMPK)-dependent, small molecule stimulation or inhibition of AMPK was performed. AMPK inhibition decreased GPER1 accumulation in cells grown in low [D-glucose] while the AMPK-activating compound AICAR ...

TY - JOUR. T1 - LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. AU - Lizcano, Jose M.. AU - Goransson, Olga. AU - Toth, Rachel. AU - Deak, Maria. AU - Morrice, Nick A.. AU - Boudeau, Jerome. AU - Hawley, Simon. AU - Udd, Lina. AU - Makela, Tomi P.. AU - Hardie, D. Grahame. AU - Alessi, Dario R.. N1 - dc.publisher: Nature Publishing Group PY - 2004/2. Y1 - 2004/2. N2 - We recently demonstrated that the LKB1 tumour suppressor kinase, in complex with the pseudokinase STRAD and the scaffolding protein MO25, phosphorylates and activates AMP-activated protein kinase (AMPK). A total of 12 human kinases (NUAK1, NUAK2, BRSK1, BRSK2, QIK, QSK, SIK, MARK1, MARK2, MARK3, MARK4 and MELK) are related to AMPK. Here we demonstrate that LKB1 can phosphorylate the T-loop of all the members of this subfamily, apart from MELK, increasing their activity ,50-fold. LKB1 catalytic activity and the presence of MO25 and STRAD are required for activation. Mutation of the ...

Several new studies show that curcumin activates the enzyme AMPK, along with related fat burning gene signals, thus preventing the build up of fat in liver cells. AMPK (AMP-activated protein kinase) is a pivotal cell enzyme required to orchestrate the burning of fat and sugar. The first study was trying to figure out if curcumin had a mechanism that could specifically help protect against non-alcohol fatty liver disease; a common consequence of obesity-related health problems. …. ...

The RN− (rendement Napole, French for Napole yield) phenotype is common in Hampshire pigs and is characterized by a 70% increase in glycogen content in skeletal muscle and large effects on meat characteristics (pH, water content, technological yield and lean meat content). The phenotype is controlled by an autosomal dominant allele designated RN−. The protein kinase AMP-activated γ3 subunit gene, PRKAG3, which encodes the γ3 isoform of AMP-activated protein kinase (AMPK), was identified as the causative gene for this phenotype by a pure positional cloning approach. There are now several lines of evidence supporting our interpretation that the RN− phenotype is caused by a missense mutation (Arg200→Gln) in PRKAG3. Recent data from another group have revealed the presence of a third functional allele at the PRKAG3 locus, probably caused by a Val199→Ile missense mutation. This allele has opposite effects compared with RN, as it is associated with a low glycogen content. We have confirmed ...

Recent population-based studies of type 2 diabetes patients have reported that metformin treatment is associated with a reduced cancer incidence and mortality ( 19, 20). Here, we investigated whether metformin has a direct effect on growth of HCT116 colon cancer cells in vivo. We report that treatment with either metformin or AICAR, two known activators of AMPK, reduces tumor growth in xenografts of HCT116 cells deficient for p53. In contrast, metformin and AICAR have little to no effect on the growth of xenografts of HCT116 p53+/+ cells. This selectivity correlated with the ability of HCT116 and untransformed MEFs to engage in a p53-dependent metabolic response that promoted cell survival.. p53 is a tumor suppressor that is often mutated in cancer. In response to genotoxic stresses, p53 induces a transcriptional response that can result in cell cycle arrest, senescence, or apoptosis. However, a recent study revealed a prosurvival role for p53 in cells metabolically impaired by glucose ...

Uncoupling protein 3 (UCP3) is a mitochondrial membrane transporter that is expressed mainly in skeletal muscle where it plays an important role in energy expenditure and fat oxidation. In this study, we investigated the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on UCP3 gene expression in C2C12 muscle cells. EPA and DHA up-regulated UCP3 mRNA level in a dose-dependent manner and similarly increased UCP3 promoter activity in C2C12 muscle cells. To determine whether AMP-activated protein kinase (AMPK) signaling may also directly regulate UCP3 expression, 5′-amino-4-imidazolecarboxamide-ribonucleoside (AICAR), an AMP analog that activates AMPK, was treated in C2C12 muscle cells. AICAR showed additive effects with EPA or DHA on the UCP3 promoter activation. These results indicate that EPA and DHA directly regulate the gene expression of UCP3, potentially through AMPK-mediated pathway in C2C12 muscle cells.

Our results show that, even in LKB1-null tumor cells, activation of AMPK is sufficient for cell-cycle arrest, and necessary for the arrest induced by Ca2+-elevating agents. Inhibition of cell proliferation and G1 arrest in response to AMPK activation has been demonstrated previously in cells expressing LKB1 (12-14). However, those studies relied on the use of the pharmacologic activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), which can have AMP-independent off-target effects (42), or on overexpression of activated AMPK, which might also lead to nonphysiologic effects. Our results show that the G1 arrest (25) and consequent inhibition of proliferation (24) caused by the reexpression of LKB1 in LKB1-null tumor cells is mediated by AMPK and not by any of the AMPK-related kinases (ARK). We have previously shown that the ARKs that have detectable activity in HeLa cells, that is, SIK1, SIK2, SIK3, NUAK2, MARK1, MARK2/3, and MARK4, were (unlike AMPK) not activated in the cells by ...

The aim of the present study was to determine whether the endothelial dysfunction associated with CAD (coronary artery disease) and T2D (Type 2 diabetes mellitus) is concomitant with elevated mtROS (mitochondrial reactive oxygen species) production in the endothelium and establish if this, in turn, regulates the activity of endothelial AMPK (AMP-activated protein kinase). We investigated endothelial function, mtROS production and AMPK activation in saphenous veins from patients with advanced CAD. Endothelium-dependent vasodilation was impaired in patients with CAD and T2D relative to those with CAD alone. Levels of mitochondrial H 2 O 2 and activity of AMPK were significantly elevated in primary HSVECs (human saphenous vein endothelial cells) from patients with CAD and T2D compared with those from patients with CAD alone. Incubation with the mitochondria-targeted antioxidant, MitoQ 10 significantly reduced AMPK activity in HSVECs from patients with CAD and T2D but not in cells from patients with ...

BACKGROUND Cytotoxic T lymphocyte antigen 4 (CTLA4) is essential for immune homeostasis. Genetic mutations causing haploinsufficiency (CTLA4h) lead to a phenotypically heterogenous, immune-mediated disease that can include neuroinflammation. The neurological manifestations of CTLA4h are poorly characterized.METHODS We performed an observational natural history study of 50 patients with CTLA4h who were followed at the NIH. We analyzed clinical, radiological, immunological, and histopathological data.RESULTS Evidence for neuroinflammation was observed in 32% (n = 16 of 50) of patients in this cohort by magnetic resonance imaging (MRI) and/or by cerebrospinal fluid analysis. Clinical symptoms were commonly absent or mild in severity, with headaches as the leading complaint (n = 13 of 16). The most striking findings were relapsing, large, contrast-enhancing focal lesions in the brain and spinal cord observed on MRI. We detected inflammation in the cerebrospinal fluid and leptomeninges before the ...

PRIOR TO HAVING A BABY BOTH PARENTS SHOULD DO 6-12 MONTHS OF DETOXING!!! XENOESTROGENS SHOW UP IN CHILDREN AS OBESITY, DSLEXIA, HYPER ACTIVITY & MEMORY DISORDERS…. Pine Pollen (data from the lost empire). 1. Prostate. Its hard to find a natural supplement which has a positive influence on two completely opposite conditions. Pine Pollen contains Gibberlins, which is a naturally occurring plant steroid, that helps in reducing or enlarging the prostate, depending on what seems to be the problem.. 2. Anti-inflammatory properties. Gibberlins in Pine Pollen are in charge of fighting cancerous cells and also provide an anti-inflammatory effect. For this and other reasons, Pine Pollen is often used to treat various inflammatory processes.. 3. Helps Liver Cleansing. Apart from other plant steroids, Pine Pollen also contains brassinosteroid brassinolide which proved to be very useful in helping the liver get rid off xenobiotics, chemical built ups in the body.. 4. Immune System Boost. Pine Pollen and ...

Binding of adiponectin to ADIPOR1 results in activation of an AMP-dependent kinase (AMPK) signaling pathway that regulates fatty acid oxidation and insulin sensitivity. ADIPOR1 is also known as progestin and adipoQ receptor family member I (PAQR1), CGI45, ACDCR1, and TESBP1A.. Binding of adiponectin to ADIPOR2 mediates increased AMP-activated protein kinase (AMPK) activity, peroxisome proliferator-activated receptor-alpha (PPAR-alpha) ligand activity, fatty acid oxidation, and glucose uptake. ADIPOR2 is also known as progestin and adipoQ receptor family member II (PAQR2), and ACDCR2. ...

Binding of adiponectin to ADIPOR1 results in activation of an AMP-dependent kinase (AMPK) signaling pathway that regulates fatty acid oxidation and insulin sensitivity. ADIPOR1 is also known as progestin and adipoQ receptor family member I (PAQR1), CGI45, ACDCR1, and TESBP1A.. Binding of adiponectin to ADIPOR2 mediates increased AMP-activated protein kinase (AMPK) activity, peroxisome proliferator-activated receptor-alpha (PPAR-alpha) ligand activity, fatty acid oxidation, and glucose uptake. ADIPOR2 is also known as progestin and adipoQ receptor family member II (PAQR2), and ACDCR2. ...

Arabidopsis contains 38 protein kinases that are related to SNF1 from yeast (Table IV). The SnRKs form three subgroups based on sequence similarity and domain structure (Fig. 1). The SnRK1 subgroup is the most closely related to SNF1 from yeast and to AMP-activated protein kinases (AMPK) from animals (Fig. 2). Only three Arabidopsis sequences belong to the SnRK1 subgroup. On average, these are the largest proteins in the SnRK group with molecular mass values from 56.7 to 58.7 kD. Studies of the biochemistry and physiology of SnRK1s from crop plants have suggested that, like SNF1 and AMPK, they may regulate metabolism in response to nutritional or environmental stress (for review, see Halford and Hardie, 1998; Halford et al., 2000, 2003; Hardie, 2000). Unlike AMPK, SnRK1s are not allosterically regulated by AMP; however, AMP indirectly regulates the activity of a spinach SnRK1 via a mechanism that involves regulation of the phosphorylation/dephosphorylation of a residue in the enzymes activation ...

The mechanism whereby lactic acid bacteria extend the life-span of has previously been elucidated. worms. Furthermore mutations in or did not alter lifespan extension compared with wild-type failed to display lifespan extension in loss-of-function mutants of and species extend lifespan by activating DAF-16 via the c-Jun N-terminal kinase (JNK) pathway which is related to stress response and the AMP-activated protein kinase (AMPK)-pathway that is activated by dietary restriction. species are lactic acid bacteria that have only recently been classified as a new genus. Serpinf2 species are found in fermented foods including Korean traditional fermented vegetables and kimchi sugar cane and the intestinal tracts of humans and other animals1. Fermented foods including kimchi possess diverse lactic acid bacteria the composition of which effects fermentation and the sensory properties of kimchi2. Kimchi is a well-known probiotic food with INK 128 similar health benefits to probiotic yogurt. Additionally ...

Rabbit polyclonal antibody raised against synthetic phosphopeptide of PRKAA1. Synthetic phosphopeptide corresponding to residues surrounding S79 of Carassius auratus PRKAA1. (PAB12747) - Products - Abnova

Hypoxic chemotransduction in the carotid body requires release of excitatory transmitters from type I cells that activate afferent sensory neurones. Transmitter release is dependent on voltage-gated Ca2+ entry which is evoked by membrane depolarization. This excitatory response to hypoxia is initiated by inhibition of specific O2 sensitive K+ channels, of which several types have been reported. Here, we discuss mechanisms which have been put forward to account for hypoxic inhibition of type I cell K+ channels. Whilst evidence indicates that one O2 sensitive K+ channel, BKCa, may be regulated by gasotransmitters (CO and H2S) in an O2-dependent manner, other studies now indicate that activation of AMP-activated protein kinase (AMPK) accounts for inhibition of both BKCa and leak O2 sensitive K+ channels, and perhaps also other O2sensitive K+ channels reported in different species. We propose that type I cell AMPK activation occurs as a result of inhibition of mitochondrial oxidative phosphorylation, and

Several new studies show that curcumin activates the enzyme AMPK, along with related fat burning gene signals, thus preventing the build up of fat in liver cells. AMPK (AMP-activated protein kinase) is a pivotal cell enzyme required to orchestrate the burning of fat and sugar. The first study was trying to figure out if curcumin had a mechanism that could specifically help protect against non-alcohol fatty liver disease; a common consequence of obesity-related health problems. This study showed that curcumin turned on AMPK, induced fat burning, while inhibiting fat deposition in liver cells. The researchers concluded that these mechanisms were adequate to conclude that, curcumin extract may be active in the prevention of fatty liver.. In a second study, researchers fed a high fat diet to mice to the point of inducing fatty liver. In the mice that were also fed curcumin, it prevented the mice from developing fatty liver. It did this by activating A…. Read More ...

Abstract. Starting from a kinase of interest, AMP-activated protein kinase (AMPK) has gone far beyond an average biomolecule. Being expressed in all mammalian cell types and probably having a counterpart in every eukaryotic cell, AMPK has attracted interest in virtually all areas of biological research. Structural and biophysical insights have greatly contributed to a molecular understanding of this kinase. From good old protein biochemistry to modern approaches, such as systems biology and advanced microscopy, all disciplines have provided important information. Thus, multiple links to cellular events and subcellular localizations have been established. Moreover, the crucial involvement of AMPK in human health and disease has been evidenced. AMPK accordingly has moved from an interesting enzyme to a pharmacological target. However, despite our extensive current knowledge about AMPK, the growing community is busier than ever. This book provides a snapshot of recent and current AMPK research with ...

Adiponectin is a fat tissue-derived adipokine with beneficial effects against diabetes, cardiovascular diseases, and cancer. Accordingly, adiponectin-mimetic molecules possess significant pharmacological potential. Oligomeric states of adiponectin appear to determine its biological activity. We identified a highly conserved, 13-residue segment (ADP-1) from adiponectins collagen domain which comprises GXXG motifs and has one asparagine and two histidine residues that assist in oligomeric protein assembly. We therefore hypothesized that ADP-1 promotes oligomeric assembly and thereby mediates potential metabolic effects. We observed here that ADP-1 is stable in human serum and oligomerizes in aqueous environments. We also found that ADP-1 activates AMP-activated protein kinase (AMPK) in an adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1)-dependent pathway and stimulates glucose uptake in rat skeletal muscle cells (L-6 myotubes). ADP-1-induced glucose ...

PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. May also phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165).

The browser then sends a request to the serveriron nat server, which then sends an answer; this could be, for example, an HTML page. The patients neutrophils extended a few fork-like pseudopodia and actin isolated from his neutrophils polymerized netserver agents in vitro. Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398. The server I have is KVM though and another one XenHVM. AIP1Alix may be subject to similar regulation in cells. In addition, the search engine will boost up your site ranking in Canada when you host with a Canada hosting service. Our servers have been the stepping stone in the success of many of our small businesses and netserver agents global enterprise clients. We are going to generate a few strong passwords netserver agents When you netserver agents running multiple WordPress sites, it becomes very difficult remembering netserver agents the various sites ...

Authors: Melissa M Thomas, David C Wang, Donna M DSouza, Matthew P Krause, Andrew S Layne, David S Criswell, Hayley M ONeill, Michael K Connor, Judy E Anderson, Bruce E Kemp, Gregory R Steinberg, Thomas J Hawke

Sigma-Aldrich offers abstracts and full-text articles by [Chiara Zucal, Vito G DAgostino, Antonio Casini, Barbara Mantelli, Natthakan Thongon, Debora Soncini, Irene Caffa, Michele Cea, Alberto Ballestrero, Alessandro Quattrone, Stefano Indraccolo, Alessio Nencioni, Alessandro Provenzani].

The technology segment of the cell signaling market includes microscopy, western blotting, immunohistochemistry (IHC), flow cytometry, enzyme-linked immunosorbent assay (ELISA), mass spectrometry, and other technologies (immunofluorescence and immunoprecipitation). The microscopy segment is estimated to account for the largest share of the cell signaling market in 2017. On the basis of the pathway, the cell signaling market is categorized into Akt, AMP-activated protein kinase (AMPK), ErbB/HER, Hedgehog (Hh), Janus kinase and signal transducer and activator of transcription (JAK/STAT), NF-κB, Notch, and other signaling pathways. In 2017, the Akt segment is estimated to account the largest share of the cell signaling market. The application segment of cell signaling market includes research applications (cancer research, immunology research, stem cells research, and other research applications) and medical applications. The research applications segment is estimated to account for the largest ...

Many vascular disease states such as diabetes and hypertension are strongly associated with increased levels of reactive oxygen species (ROS) in the vascular wall, a cellular state known as oxidative stress that is often associated with a decrease in vascular .NO bioavailability. All cellular compartments posses several antioxidant enzymes responsible of controlling intracellular ROS levels. In the last decade, it has become clear that ROS, and particularly hydrogen peroxide (H2O2), may play physiological and not only pathological roles and they have been identified as key physiological-signaling mediators controlling a broad array of cellular responses. However, the precise molecular mechanisms through which H2O2 alter specific enzymatic activities in vivo remain less well understood. Protein thiols can undergo reversible modifications in the presence of H2O2 representing attractive targets for redox-signaling pathways. Previous studies of my lab demonstrated that AMP-activated protein kinase ...

PRKAA2 (Thr172) Antibody (Center), Peptide Affinity Purified Rabbit Polyclonal Antibody (Pab) validated in WB, IHC-P, FC, E (AP10846a), Abgent

Friedreichs ataxia (FRDA) is a mitochondrial rare disease, which molecular origin is associated with defect in the expression of frataxin. The pathological consequences are degeneration of nervous system structures and cardiomyopathy with necrosis and fibrosis, among others.. Differential Expression of PGC-1α and Metabolic Sensors Suggest Age-Dependent Induction of Mitochondrial Biogenesis in Friedreich Ataxia Fibroblasts. ...

Background: 17-β-estradiol has been shown to play an important role in regulating vascular function and vasomotor tone. We have previously demonstrated sex differences in rapid estrogen receptor signaling during vascular relaxation. We recently observed that estrogen activates AMPK-activated protein kinase (AMPK), suggesting that AMPK is a likely mediator of estrogen receptor (ER) signaling in vasomotor function. AMPK has been reported to participate in vascular relaxation. Furthermore, our recent studies found that incubating vascular rings with 5-aminoimidazole-4-carboxamide (AICAR), an AMPK activator, results in greater vasorelaxation of female C57BL/6J mouse vessels when compared with male vessels. However, the precise mechanisms involving estrogen receptor signaling and AMPK in promoting vascular relaxation remain unknown.. Methods and Results: To elucidate a critical role of ERα-AMPK signaling and downstream targets involved in vascular relaxation, including the potential sex difference ...

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Glioblastoma is the most aggressive type of brain cancer with the median survival time of one year. A particular microRNA, miR-451, and its counterpart, AMPK complex are known to play a key role in controlling a balance between rapid proliferation and aggressive invasion in response to metabolic stress in the microenvironment. The present paper develops a hybrid model of glioblastoma that identifies a key mechanism behind the molecular switches between proliferative phase and migratory phase in response to metabolic stress and biophysical interaction between cells. We focus on the core miR-451-AMPK control system and show how up- or down-regulation of components in these pathways affects cell proliferation and migration. The model predicts the larger window of bistable systems when there exists a time delay in the inhibitory pathway from CAB39/LKB1/STRAD/AMPK to miR-451. Delayed down-regulation of miR-451 along this pathway would let glioma cells stay longer in the proliferative stage despite ...

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Mitochondria are important cellular organelles that maintain cellular energy balance. See mitochondrial markers, the citric acid cycle, fusion, autophagy translation and more.

Deregulation of glucose and lipid metabolism in peripheral tissues is a hallmark of type 2 diabetes. AMP- activated protein kinase (AMPK) is a master regulator...